Sleep deprivation has detrimental metabolic consequences. Osteopenia and sarcopenia usually occur together and increase risk of fractures and disease. Results from studies linking sleep parameters to ...osteopenia or sarcopenia are scarce and inconsistent.
To examine the associations of sleep parameters with osteopenia and sarcopenia, considering the influence of sex and menopause.
Cross-sectional analysis of 915 participants (45-65 years, 56% women, BMI 26 (range: 18-56) kg/m2) in the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort study. Sleep duration, quality, and timing were assessed with the Pittsburgh Sleep Quality Index (PSQI); bone mineral density and relative appendicular muscle mass were measured by DXA scans. Linear and logistic regressions were performed to associate sleep parameters to bone mineral density, relative appendicular muscle mass, osteopenia (t-score between -1 and -2.5) and sarcopenia (1 SD below average muscle mass).
After adjustment for confounding factors, one unit increase in PSQI score (OR and 95% CI, 1.09, 1.03-1.14), declined self-rated sleep quality (1.76, 1.03-3.01), sleep latency (1.18, 1.06-1.31), and a one hour later sleep timing (1.51, 1.08-2.11), but not sleep duration (1.05, 0.90-1.23), were associated with osteopenia. PSQI score (1.10, 1.02-1.19) was also associated with sarcopenia; OR's of sleep latency and later mid-sleep time with sarcopenia were 1.14 (0.99-1.31) and 1.54 (0.91-2.61), respectively. Associations were somewhat stronger in women and varied per menopausal status.
These results suggest that decreased sleep quality and a later sleep timing are risk factors for osteopenia and sarcopenia in middle aged individuals.
Objective
This study aimed to investigate microvascular differences in individuals with obesity at risk for developing cardiovascular disease.
Methods
In this cross‐sectional Netherlands Epidemiology ...of Obesity study, participant sublingual microcirculation was assessed with a newly developed GlycoCheck software (Microvascular Health Solutions Inc., Salt Lake City, Utah), which integrates red blood cell velocity within the smallest capillaries (4‐7 µm) and feed vessels (>10 µm). Framingham Risk Score was used to calculate 10‐year cardiovascular risk, divided into low‐, intermediate‐, and high‐risk groups. ANOVA was used to evaluate microvascular differences among the groups.
Results
A total of 813 participants were included. The high‐risk group (n = 168) was characterized by differences in the microvasculature compared with the low‐risk group (n = 392): the high‐risk group had a 49% reduction in the number of smallest capillaries and a 9.1‐µm/s (95% CI: 5.2‐12.9) higher red blood cell velocity in the feed vessels. No differences in velocity‐corrected perfused boundary regions were found.
Conclusions
It was observed that, with adding red blood cell velocity to the software, sidestream dark field imaging is able to detect microcirculatory differences in a cohort of individuals with obesity at risk for developing cardiovascular disease.
In traditional Kaplan–Meier or Cox regression analysis, usually a risk factor measured at baseline is related to mortality thereafter. During follow-up, however, things may change: either the effect ...of a fixed baseline risk factor may vary over time, resulting in a weakening or strengthening of associations over time, or the risk factor itself may vary over time. In this paper, short-term versus long-term effects (so-called time-dependent effects) of a fixed baseline risk factor are addressed. An example is presented showing that underweight is a strong risk factor for mortality in dialysis patients, especially in the short run. In contrast, overweight is a risk factor for mortality, which is stronger in the long run than in the short run. In addition, the analysis of how time-varying risk factors (so-called time-dependent risk factors) are related to mortality is demonstrated by paying attention to the pitfall of adjusting for sequelae. The proper analysis of effects over time should be driven by a clear research question. Both kinds of research questions, that is those of time-dependent effects as well those of time-dependent risk factors, can be analyzed with time-dependent Cox regression analysis. It will be shown that using time-dependent risk factors usually implies focusing on short-term effects only.
Excess visceral fat increases the risk of type 2 diabetes and cardiovascular disease and is influenced by sex hormones. Our aim was to investigate changes in visceral fat and the ratio of visceral ...fat to total body fat (VAT/TBF) and their associations with changes in lipids and insulin resistance after 1 year of hormone therapy in trans persons.
In 179 trans women and 162 trans men, changes in total body and visceral fat estimated with dual-energy X-ray absorptiometry before and after 1 year of hormone therapy were related to lipids and insulin resistance homeostatic model assessment of insulin resistance (HOMA-IR) with linear regression analysis.
In trans women, total body fat increased by 4.0 kg (95% CI 3.4, 4.7), while the amount of visceral fat did not change (-2 grams; 95% CI -15, 11), albeit with a large range from -318 to 281, resulting in a decrease in the VAT/TBF ratio of 17% (95% CI 15, 19). In trans men, total body fat decreased with 2.8 kg (95% CI 2.2, 3.5), while the amount of visceral fat did not change (3 g; 95% CI -10, 16; range -372, 311), increasing the VAT/TBF ratio by 14% (95% CI 10, 17). In both groups, VAT/TBF was not associated with changes in blood lipids or HOMA-IR.
Hormone therapy in trans women and trans men resulted in changes in VAT/TBF, mainly due to changes in total body fat and were unrelated to changes in cardiometabolic risk factors, which suggests that any unfavorable cardiometabolic effects of hormone therapy are not mediated by changes in visceral fat or VAT/TBF.
Abstract
Context
Liver fat content and visceral fat volume are associated with insulin resistance and cardiovascular disease and are higher in men than in women.
Objective
To determine the effect of ...estradiol and testosterone treatment on liver fat and visceral fat in transgender persons.
Design
Open-label intervention study (SHAMVA) with a 1-year follow-up.
Setting
Gender clinic in a hospital.
Patients
8 trans women and 18 trans men receiving hormone treatment.
Interventions
Trans women received an antiandrogen and after 6 weeks estradiol was added. Trans men were randomized to receive triptorelin, testosterone, and anastrozole for 12 weeks or triptorelin and testosterone for 12 weeks, followed by only testosterone until week 52.
Main outcome measures
Liver fat content, visceral and abdominal subcutaneous fat volume, measured by magnetic resonance spectrometry or imaging at baseline, 6, 8, 18, and 58 weeks in transwomen or at baseline; at 6 and 12 weeks in trans men with anastrozole; and at 52 weeks in trans men without anastrozole.
Results
In trans women, liver fat content decreased by 1.55% (−2.99 to −0.12) after 58 weeks, compared to week 6. Visceral fat did not change. In trans men with anastrozole, the liver fat content and visceral fat volume did not change. In trans men without anastrozole, after 52 weeks, liver fat content increased by 0.83% (0.14 to 1.52) and visceral fat volume increased by 34% (16 to 51).
Conclusions
Sex hormones regulate liver fat content and visceral fat in men and women.
Aims/hypothesis
We hypothesised that the insulin-sensitising effect of physical activity depends on the timing of the activity. Here, we examined cross-sectional associations of breaks in sedentary ...time and timing of physical activity with liver fat content and insulin resistance in a Dutch cohort.
Methods
In 775 participants of the Netherlands Epidemiology of Obesity (NEO) study, we assessed sedentary time, breaks in sedentary time and different intensities of physical activity using activity sensors, and liver fat content by magnetic resonance spectroscopy (
n
=256). Participants were categorised as being most active in the morning (06:00–12:00 hours), afternoon (12:00–18:00 hours) or evening (18:00–00:00 hours) or as engaging in moderate-to-vigorous-physical activity (MVPA) evenly distributed throughout the day. Most active in a certain time block was defined as spending the majority (%) of total daily MVPA in that block. We examined associations between sedentary time, breaks and timing of MVPA with liver fat content and HOMA-IR using linear regression analyses, adjusted for demographic and lifestyle factors including total body fat. Associations of timing of MVPA were additionally adjusted for total MVPA.
Results
The participants (42% men) had a mean (SD) age of 56 (4) years and a mean (SD) BMI of 26.2 (4.1) kg/m
2
. Total sedentary time was not associated with liver fat content or insulin resistance, whereas the amount of breaks in sedentary time was associated with higher liver fat content. Total MVPA (−5%/h 95% CI −10%/h, 0%/h) and timing of MVPA were associated with reduced insulin resistance but not with liver fat content. Compared with participants who had an even distribution of MVPA throughout the day, insulin resistance was similar (−3% 95% CI −25%, 16%) in those most active in morning, whereas it was reduced in participants who were most active in the afternoon (−18% 95% CI −33%, −2%) or evening (−25% 95% CI −49%, −4%).
Conclusions/interpretation
The number of daily breaks in sedentary time was not associated with lower liver fat content or reduced insulin resistance. Moderate-to-vigorous activity in the afternoon or evening was associated with a reduction of up to 25% in insulin resistance. Further studies should assess whether timing of physical activity is also important for the occurrence of type 2 diabetes.
Graphical abstract
•Leptin and adiponectin concentrations differ between women and men.•Sex differences in leptin are completely explained by total body fat.•Visceral fat only partly explains sex differences in ...adiponectin.•In 44 women, we observed extreme leptin concentrations of >100 μg/L.
It is debated whether sex differences in adiponectin and leptin are due to sex differences in body fat distribution. In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, associations of measures of body fat and sex with serum adiponectin and leptin concentrations were examined using linear regression analysis (n = 6494, VAT: n = 2516). Sex differences were additionally adjusted for the measure of body fat that was most strongly associated with adiponectin or leptin concentrations. Median adiponectin concentrations in women and men were 10.5 mg/L (IQR, interquartile range: 7.7–13.9) and 6.1 mg/L (IQR: 4.5–8.2), mean difference 4.6 mg/L (95% CI: 4.3, 4.9). Median leptin concentrations in women and men were 19.2 μg/L (IQR: 11.5–30.0) and 7.1 μg/L (IQR: 4.6–11.1), mean difference 15.1 μg/L (95% CI: 14.4, 15.8). VAT was most strongly associated with adiponectin, total body fat percentage was most strongly associated with leptin. After adjustment for VAT, women had 3.8 mg/L (95% CI: 3.3, 4.3) higher adiponectin than men. After adjustment for total body fat percentage, leptin concentrations in women were 0.4 μg/L lower than in men (95% CI: −1.2, 2.0). One genetic variant (rs4731420) was associated with extreme leptin concentrations (>100 μg/L) in women: odds ratio 2.8 (95% CI: 1.7, 4.6). Total body fat percentage was strongly associated with leptin concentrations. Higher leptin concentrations in women than in men were completely explained by differences in total body fat percentage. Visceral fat was associated with adiponectin concentrations, and did not completely explain higher adiponectin concentrations in women than in men.
Background and Aims
Non‐alcoholic fatty liver disease (NAFLD) is characterized by the pathological accumulation of triglycerides in hepatocytes and is associated with insulin resistance, atherogenic ...dyslipidaemia and cardiometabolic diseases. Thus far, the extent of metabolic dysregulation associated with hepatic triglyceride accumulation has not been fully addressed. In this study, we aimed to identify metabolites associated with hepatic triglyceride content (HTGC) and map these associations using network analysis.
Methods
To gain insight in the spectrum of metabolites associated with hepatic triglyceride accumulation, we performed a comprehensive plasma metabolomics screening of 1363 metabolites in apparently healthy middle aged (age 45–65) individuals (N = 496) in whom HTGC was measured by proton magnetic resonance spectroscopy. An atlas of metabolite–HTGC associations, based on univariate results, was created using correlation‐based Gaussian graphical model (GGM) and genome scale metabolic model network analyses. Pathways associated with the clinical prognosis marker fibrosis 4 (FIB‐4) index were tested using a closed global test.
Results
Our analyses revealed that 118 metabolites were univariately associated with HTGC (p‐value <6.59 × 10−5), including 106 endogenous, 1 xenobiotic and 11 partially characterized/uncharacterized metabolites. These associations were mapped to several biological pathways including branched amino acids (BCAA), diglycerols, sphingomyelin, glucosyl‐ceramide and lactosyl‐ceramide. We also identified a novel possible HTGC‐related pathway connecting glutamate, metabolonic lactone sulphate and X‐15245 using the GGM network. These pathways were confirmed to be associated with the FIB‐4 index as well. The full interactive metabolite‐HTGC atlas is provided online: https://tofaquih.github.io/AtlasLiver/.
Conclusions
The combined network and pathway analyses indicated extensive associations between BCAA and the lipids pathways with HTGC and the FIB‐4 index. Moreover, we report a novel pathway glutamate‐metabolonic lactone sulphate‐X‐15245 with a potential strong association with HTGC. These findings can aid elucidating HTGC metabolomic profiles and provide insight into novel drug targets for fibrosis‐related outcomes.
Obesity is a risk factor for the development of asthma. In patients with obesity the diagnosis of asthma is often based on symptoms, but without objective measurements. Nevertheless, ...obesity-associated asthma is recognized as a distinct asthma phenotype. Therefore, this study explores lung function and symptoms in asthma patients with and without obesity.
The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort study with 6671 participants (aged 45-65 years) of whom 472 had asthma. Of this latter group, linear regression analysis was used to examine differences in lung function and symptoms between asthma patients with (n = 248) and without obesity (n = 224), and between asthma patients with and without increased Fe
. Analyses were adjusted for confounders.
Asthma patients with obesity had lower predicted FEV
and FVC values than patients without obesity adjusted mean difference (MD) -3.3% predicted, 95% CI -6.5, -0.2; adjusted MD -5.0% predicted, 95% CI -7.8, -2.1. The prevalence of symptoms was higher in patients with obesity. Asthma patients with obesity and with increased Fe
had lower FEV
and FEV
/FVC values compared with those with low Fe
(adjusted MD -6.9% predicted, 95% CI -11.7, -2.0; -2.4%, 95% CI -4.6, -0.2).
Asthma patients with obesity had lower FEV
and FVC values than patients without obesity. This suggests that patients with obesity have restrictive lung function changes, rather than obstructive changes. Asthma patients with obesity and increased Fe
showed more obstructive changes. Fe
might help to identify patients with eosinophilic inflammation-driven asthma, whereas patients with low Fe
might have an obesity-associated asthma phenotype in which symptoms are partly caused by the obesity.
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